NKTR-181 may represent a safe and effective analgesic for patients with chronic low back pain, according to a study published in Pain.
NKTR-181 is a full µ-opioid receptor agonist that was shown to have a delayed rate of entry through the blood-brain barrier, thus reducing its abuse potential. After a ≤3-week screening period, study participants were titrated for NKTR-181 for 3 to 7 weeks, after which they were randomly assigned to receive the drug or placebo. For titration, a total of 1189 patients with moderate to severe chronic low back pain refractory to non-opioid analgesics received NKTR-181 twice-daily for 1 week, starting at a 100-mg dose. Those who tolerated treatment underwent titration to a dose that provided pain relief and was associated with acceptable side effects. Increases in treatment dose occurred each week to a maximum twice-daily dose of 400 mg. Treatment efficacy was defined as a consistent weekly 7-day mean pain score ≤4 and daily scores ≤4 on ≥5 days per week. Treatment efficacy was also defined as the need for rescue medications on ≤2 days per week with a ≥2-point reduction in weekly pain score. Patients who met efficacy criteria were randomly assigned to receive NKTR-181 (n=309) or placebo (n=301).
During the open-label NKTR-181 titration period, there was a mean reduction in pain score from 6.73 at baseline to 2.32. The least-squares mean change in pain score in patients treated with NKTR-181 was 0.92 vs 1.46 for those receiving placebo after randomization (P =.002). The rate of ≥30% improvement was 71.2% vs 57.1% in patients treated with NKTR-181 vs placebo, respectively (P <.001). The ≥50% improvement responder rate was also higher in patients receiving NKTR-181 vs placebo (51.1% vs 37.9%, respectively; P =.001).
The open-label design and the sole inclusion of patients in the double-blind phase who tolerated NKTR-181 represent study limitations.
“In recent years, the US Food and Drug Administration has encouraged the development of abuse-deterrent formulations of opioid analgesics. Efforts to convert NKTR-181 into a more active µ-opioid receptor agonist or one that crosses the blood-brain barrier at a faster rate using known chemical or physical methods have been unsuccessful,” noted the study authors.
Markman J, Gudin J, Rauck R, et al. Summit-07: a randomized trial of NKTR-181, a new molecular entity, full mu-opioid receptor agonist for chronic low-back pain [published online February 8, 2019]. Pain. doi: 10.1097/j.pain.0000000000001517